Pathogenesis and Treatment of Type 2 Diabetic Nephropathy: Lessons from the Spontaneous KK/Ta Mouse Model

摘要

Diabetic nephropathy is a major cause of end-stage renal failure (ESRF) in patients with both type 1 and type 2ndiabetes. Many factors such as genetic and non-genetic promoters, hypertension, hyperglycemia, accumulation ofnadvanced glycation end products (AGEs), dyslipidemia, albuminuria and proteinuria influence the progression of thisndesease. It is important to determine pathogenesis and treatment of this disease. However, it is difficult to investigate sincenhuman diabetes is a heterogeneous and multifactorial disease. Therefore, most of these mechanisms have beenninvestigated in animal experiments. KK/Ta mice have a clearly different genetic background in terms of body weight,nblood glucose, impaired glucose tolerance (IGT), urinary albumin excretion and serum triglyceride than BALB/c mice.nRenal lesions of KK/Ta mice closely resemble those in human early diabetic nephropathy. Thus, the KK/Ta mouse maynserve as a suitable model for the study of type 2 diabetes and early diabetic nephropathy in humans. We reviewed geneticnsusceptibility using genome-wide linkage analysis and differential display polymerase chain reaction (DD-PCR) ornNorthern blot analysis, and treatment of diabetic nephropathy using angiotensin type 1 (AT1) receptor blockers (ARB) ornthiazolidinediones (TZDs) in KK/Ta mice.